Midazolam for conscious sedation during pediatric oncology procedures: safety and recovery parameters

Multiple bone marrow aspirations or biopsies and lumbar punctures are a necessary part of the diagnosis and treatment of many pediatric cancer patients. Pharmacologic sedation may decrease the distress associated with these procedures. Midazolam (MDZ, Versed) is a water-soluble, rapid-onset, short-duration benzodiazepine that has not been studied widely in children. We prospectively evaluated safety and recovery parameters for intravenous MDZ used for conscious sedation by oncologists (without an anesthesiologist in attendance) for 70 procedures (bone marrow aspirations, lumbar punctures, or bone marrow aspirations plus lumbar punctures) in 24 ambulatory pediatric cancer patients, aged 1.5 to 15.5 years. MDZ was used alone or in combination with morphine or fentanyl. Respiratory rate, oxygen saturation, blood pressure, and heart rate were monitored. Sedation, anxiolysis, and recovery were assessed with a behavior score and a modified recovery room discharge score. Restraint was not required in 45% of the procedures. In no case was a respiratory rate less than 12 observed. In nine procedures (13%), an oxygen saturation less than or equal to 90 occurred, all within 10 minutes after the last dose of MDZ. Ten procedures (14%) required verbal stimulation to take deeper breaths. Two patients did not respond immediately to verbal stimulation and received face-mask oxygen. Hypoxemia was not correlated with opioid use. Hypoxemia appears to be related to total MDZ dose and may occur with normal respiratory rates; all cases resolved with verbal stimulation or face-mask oxygen without specific airway maneuvers or assisted ventilation. Heart rate and blood pressure remained stable in all 70 procedures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of routine lumbar puncture in neonatal sepsis

Objective: To evaluate the utility of lumbar puncture done routinely as part of complete workup in neonatal sepsis.
Methodology: Two hundred and nine consecutive lumbar punctures performed in 169 neonates were prospectively evaluated for the diagnosis of meningitis over a 6 month period in a tertiary care referral neonatal unit.
Results: Among babies with 'suspected clinical sepsis', five (3.3%) were diagnosed to have meningitis. None of the clinically normal babies with high risk obstetric factors alone had meningitis. The lumbar puncture was traumatic in 22.9%, and in 26.3% the fluid obtained was inadequate for complete analysis. The results were inconclusive in 37% of the cases.
Conclusion: Based on this study, routine lumbar puncture may not be required in clinically normal newborns with adverse obstetric factors. In babies with clinical sepsis, though the yield is not very high; there are no reliable clinical or laboratory markers to predict which babies will have meningitis and hence these babies would warrant a lumbar puncture.     

A randomized trial of eutectic mixture of local anesthetics during lumbar puncture in newborns

OBJECTIVE: To determine the efficacy of a topical anesthetic cream, eutectic mixture of local anesthetics (EMLA), in alleviating pain associated with lumbar puncture in newborns. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Neonatal intensive care unit of a university teaching hospital.Patients Sixty consecutive newborns (gestational age, >or=34 weeks) undergoing diagnostic lumbar puncture.Intervention Topical application of 1 g of EMLA or placebo 60 to 90 minutes before lumbar puncture. MAIN OUTCOME MEASURES: Heart rate, transcutaneous oxygen saturation level, and total behavioral score recorded on a video camera and graded according to the Neonatal Facial Coding System. RESULTS: Compared with baseline, all newborns experienced pain as evidenced by increased heart rate, decreased oxygen saturation level, and total behavioral score (all within-groups differences were significant using repeated-measures analysis of variance; P<.001) during the procedure. Compared with placebo, EMLA significantly attenuated the pain response as shown by a lower mean +/- SE heart rate (per minute), particularly at needle insertion (EMLA: 159.3 +/- 2.3; placebo: 175.2 +/- 2.7; P<.001) and needle withdrawal (EMLA: 153.8 +/- 2.6; placebo: 167.3 +/- 2.5; P<.001), and a lower mean +/- SE total behavioral score, again at insertion (EMLA: 4.0 +/- 0.3; placebo: 5.0 +/- 0.0; P =.004) and withdrawal (EMLA: 1.8 +/- 0.3; placebo: 3.9 +/- 0.3; P<.001). There was no statistically significant difference between groups with regard to oxygen saturation level. CONCLUSIONS: Lumbar puncture in newborns produces pain responses. Eutectic mixture of local anesthetics is an efficacious agent for reducing the pain associated with needle insertion and withdrawal during lumbar puncture in newborns.     

Ultrasound-guided lumbar puncture in pediatric patients: technical success and safety

Background

Disadvantages of fluoroscopically guided lumbar puncture include delivery of ionizing radiation and limited resolution of incompletely ossified posterior elements. Ultrasound (US) allows visualization of critical soft tissues and the cerebrospinal fluid (CSF) space without ionizing radiation.

Objective

To determine the technical success and safety of US-guided lumbar puncture in pediatric patients.

Materials and methods

A retrospective review identified all patients referred to interventional radiology for lumbar puncture between June 2010 and June 2017. Patients who underwent lumbar puncture with fluoroscopic guidance alone were excluded. For the remaining procedures, technical success and procedural complications were assessed. Two hundred and one image-guided lumbar punctures in 161 patients were included. Eighty patients (43%) had previously failed landmark-based attempts.

Results

One hundred ninety-six (97.5%) patients underwent lumbar puncture. Five procedures (2.5%) were not attempted after US assessment, either due to a paucity of CSF or unsafe window for needle placement. Technical success was achieved in 187 (95.4%) of lumbar punctures attempted with US guidance. One hundred seventy-seven (90.3%) were technically successful with US alone (age range: 2 days-15 years, weight range: 1.9-53.1 kg) and an additional 10 (5.1%) were successful with US-guided thecal access and subsequent fluoroscopic confirmation. Three (1.5%) cases were unsuccessful with US guidance but were subsequently successful with fluoroscopic guidance. Of the 80 previously failed landmark-based lumbar punctures, 77 (96.3%) were successful with US guidance alone. There were no reported complications.

Conclusion

US guidance is safe and effective for lumbar punctures and has specific advantages over fluoroscopy in pediatric patients.

     

Successful use of nitrous oxide during lumbar punctures: A call for nitrous oxide in pediatric oncology clinics

Numerous reports describe the successful use of nitrous oxide for analgesia in children undergoing painful procedures. Although shown to be safe, effective, and economical, nitrous oxide use is not yet common in pediatric oncology clinics and few reports detail its effectiveness for children undergoing repeated lumbar punctures. We developed a nitrous oxide clinic, and undertook a review of pediatric oncology lumbar puncture records for those patients receiving nitrous oxide in 2011. No major complications were noted. Minor complications were noted in 2% of the procedures. We offer guidelines for establishing such a clinic.     

Serial lumbar punctures for at least temporary amelioration of neonatal posthemorrhagic hydrocephalus

Serial lumbar punctures for the management of neonatal posthemorrhagic hydrocephalus without intracranial hypertension were evaluated in 16 infants. Cranial ultrasonography to evaluate ventricular size and the Ladd monitor at the anterior fontanel to measure intracranial pressure were utilized immediately before and after lumbar puncture. In 12 patients, a decrease in ventricular size and in anterior fontanel pressure could be effected with each lumbar puncture. In these infants, cessation of progression of the hydrocephalus and intermittent decreases in ventricular size were accomplished. In four patients, lumbar punctures were not successful in decreasing ventricular size or lowering intracranial pressure. Two criteria could be defined to determine whether lumbar puncture could provide at least temporary benefit for the treatment of posthemorrhagic hydrocephalus. The first of these is to establish the presence of communication between lateral ventricles and lumbar subarachnoid space by effecting a decrease in ventricular size and a decrease in intracranial pressure by removal of CSF. The second criterion is to ascertain a critical volume of CSF (usually relatively large) that must be removed in order to effect the above changes. Cranial ultrasonography and measurement of intracranial pressure by application of the Ladd monitor to the anterior fontanel are extremely valuable in the evaluation of lumbar punctures in the management of posthemorrhagic hydrocephalus.     

Single-center experience with intrathecal administration of Nusinersen in children with spinal muscular atrophy type 1

Background

Spinal muscular atrophy (SMA) is a neuromuscular disorder mainly characterized by proximal muscle weakness. There have been enormous advances in therapeutic development with the possibility to influence the clinical course of the disease. Nusinersen is the first approved drug to treat SMA. It is administered intrathecally and acts as splicing modifier of the SMN2 gene.

Topical skin anesthesia for venous, subcutaneous drug reservoir and lumbar punctures in children

A new topical anesthetic ointment (EMLA, "eutectic mixture of prilocaine and lidocaine was studied in a double-blind, placebo-controlled trial to evaluate its efficiency in alleviating pain associated with venous, subcutaneous drug reservoir and lumbar punctures in children. Pain intensity was scored by the children themselves, using a visual analogue scale in which 0 corresponded to absence of sensation and 10 to the worst imaginable painful sensation. Venipunctures were performed on 18 children (6.1 to 12.2 years of age) equally divided in the study and control groups; EMLA cream was associated with lesser pain scores than those with placebo (means +/- SD: 2.8 +/- 2.4 vs 6.8 +/- 2.1, P less than .01). A crossover trial was used in the studies of subcutaneous drug reservoir and lumbar punctures, eight children (6.1 to 15.1 years of age) were tested for subcutaneous drug reservoir punctures; pain induced by this procedure was rated at 3.9 +/- 2.2 with placebo compared with 1.2 +/- 1.8 with EMLA cream (P less than .04). In lumbar punctures (14 children studied, 5.5 to 15.3 years of age), EMLA cream was again associated with less pain (1.9 +/- 1.9) than was placebo (5.6 +/- 3.0, P less than .01). It was concluded that the use of EMLA cream substantially reduces pain caused by venous, subcutaneous drug reservoir, and lumbar punctures in children and may therefore be offered to young patients, particularly those repeatedly submitted to such procedures.     

Systemic anaphylaxis following local lidocaine administration during a dental procedure

We report a 4-year-old child who developed systemic anaphylactic reaction to lidocaine hydrochloride within 15 minutes after a dental procedure. Hypersensitivity to local anesthetics is not common; however, if anaphylaxis did happen, it required emergent and immediate resuscitation. To prevent such complications, complete medical history including drug allergy should be taken. Prompt administration of epinephrine and other resuscitative measures are life saving in such circumstance. All emergency room physicians should consider systemic anaphylaxis in patients with rapid vascular collapse and respiratory failure immediately following lidocaine administration for minor outpatient procedures.     

Hypothesis: Neonatal respiratory distress may be related to asymptomatic colonization with group B streptococci

BACKGROUND: Phospholipids from the group B streptococcal (GBS) cell wall cause pulmonary hypertension in experimental animals. When exposed to penicillin, Streptococcus mutans releases phospholipids immediately. We hypothesize that newborns colonized with GBS receive bacterial phospholipids leading to pulmonary hypertension and respiratory distress, especially in the situation of newborns of penicillin-treated mothers. We examined clinical and epidemiologic data on these relations. METHODS: We used data from a prospective multicenter GBS study conducted from 1995 to 1999 in which 1674 of 17,690 newborns cultured at 4 sites were colonized with GBS. Our analyses included 1610 colonized newborns > or =32 weeks gestation without early-onset disease. Clinical features were compared between 1003 lightly colonized (GBS positive at < or =2 sites) and 607 heavily colonized (positive at 3 or 4 sites) newborns. The rates of respiratory distress were compared between colonized newborns of penicillin-treated mothers and those of untreated mothers. RESULTS: Of the 1610 colonized newborns, 8.8% had signs of respiratory distress within 48 hours after birth (cases). Oxygen supplementation was used in 60% of the cases, mechanical ventilation was required in 5% and persistent pulmonary hypertension was diagnosed in 2%. Compared with light colonization, heavy colonization increased the rate of respiratory distress 1.73-fold (95% CI, 1.26-2.38), a discharge diagnosis of respiratory disorder 2.02-fold (95% CI, 1.16-3.52), a blood/cerebrospinal fluid obtained for culture 1.54-fold (95% CI, 1.24-1.93) and antibiotic administration after birth 1.87-fold (95% CI, 1.34-2.61). Penicillin use during labor was associated with a 2.62-fold (95% CI, 1.79-3.83) increase in respiratory distress in the colonized newborn. CONCLUSIONS: Our findings support the association of neonatal respiratory distress with asymptomatic GBS colonization and with penicillin use during labor. These data require confirmation.     

存在出血风险患儿行腰椎穿刺术后3天内发生穿刺部位血肿的病例系列报告

目的探讨存在出血风险患儿行腰椎穿刺（腰穿）术是否容易发生穿刺部位血肿。方法回顾性收集首都医科大学附属北京儿童医院（我院）接受过腰穿且存在凝血功能异常（主要指有出血风险）的住院患儿的病历，排除入院至出院时间≤24 h病历，考察有出血风险时行腰穿术后3 d内是否发生穿刺部位血肿。出血风险综合指标包括：①有出血的症状和体征；②腰穿前3 d内接受过抗凝治疗、或输注过PLT或血浆；③PLT、纤维蛋白原（FIB）低于正常值下限，凝血酶原时间（PT）、部分凝血活酶时间（APTT）、抗凝酶Ⅲ（AT-Ⅲ）活性和国际标准化比值（INR）高于上限。符合①或②，合并③为有出血风险。结果2014年1月1日至2019年7月30日我院出院病历病案首页有腰穿记录并排除24 h出院病历，最终232例患儿370例次腰穿记录进入本文分析。232例患儿中，年龄4 h至17岁8个月，中位年龄为3岁。370例次腰穿中，以怀疑各种中枢神经系统感染性疾病（209例次，56.5%）和需要鞘内注射药物（142例次，38.4%）为主，无存在腰穿绝对禁忌证行腰穿病例。存在出血风险综合指标异常的患儿，即使有出血表现/抗凝药物和输注PLT史且实验室6项指标中任意指标指示出血风险［PLT 1~97(53±30)×109·L-1、PT 13~24.8(15.7±3.4) s、APTT 40.4~157.9(60.2±20.2) s、INR 1.21~2.11(1.53±0.34)、FIB 0.68~1.99(1.34±0.40) g·L-1、AT-Ⅲ130~158.6(144.3±11.7)%］，行腰穿后3 d内穿刺部位均未发生血肿。结论有出血表现、腰穿前抗凝或输血治疗、实验室出血指标异常儿童腰穿部位发生血肿风险极低。     

Regional anesthesia during newborn circumcision. Effect on infant pain response

A controlled, double-blind investigation was undertaken to determine whether regional anesthesia by dorsal penile nerve block (DPNB) could effectively minimize the pain and behavioral disruptions usually associated with newborn circumcision. Fifteen infants had DPNB with lidocaine, eight control infants had DPNB with saline, and eight additional control infants were circumcised without undergoing DPNB. Newborn distress was gauged by subjective observation, measurement of heart rate, and the percent of time spent crying in six sequential timed intervals during circumcision. Ninety-three percent of subjects who received lidocaine were observed to have a decrease in agitation after anesthetic administration. The mean increase in heart rate during circumcision was at least 50 percent less in the lidocaine injected group than in either control group (p less than 0.01). Infants who had DPNB with lidocaine cried 50 percent less during circumcision compared to combined controls (p less than 0.01). DPNB was easily administered, and there were no significant complications. Physicians who circumcise newborns have good reason to employ the technique of dorsal penile nerve block with lidocaine to minimize infant pain and distress.     

Lumbar puncture frequency and cerebrospinal fluid analysis in the neonate

A prospective study was performed to assess the frequency and diagnostic utility of lumbar punctures in neonates both during their first week of life and thereafter. During the two 6-month periods from January 1, 1985 to June 30, 1985, and February 1, 1986 to July 31, 1986, 712 neonates underwent 728 lumbar punctures during their first week of life primarily as part of the evaluation for suspected infection, either congenital or postnatal. There were eight patients with positive spinal fluid cultures in the first week of life, but only one patient simultaneously had a positive blood culture and a clinical course consistent with meningitis. In contrast, a considerably higher yield, approximating five times that of the first week of life, was obtained in patients undergoing a lumbar puncture after the first week of life.     

Role of routine investigations in children presenting with their first febrile convulsion

To assess the role of routine investigations in children presenting with their first febrile convulsion, the results of investigations carried out in 328 children over a 2-year period were reviewed. Lumber puncture was performed in 96% of cases and resulted in the detection of 4 cases of unsuspected meningitis, one of which was bacterial. 2 children had normal lumbar punctures on admission but developed meningococcal meningitis within 48 hours. Sugar, calcium, urea, and electrolyte estimations, and blood counts were commonly performed but were unhelpful. We suggest that lumbar puncture in those children presenting with their first febrile convulsion under the age of 18 months is the only useful routine investigation.     

Role of routine investigations in children presenting with their first febrile convulsion.

To assess the role of routine investigations in children presenting with their first febrile convulsion, the results of investigations carried out in 328 children over a 2-year period were reviewed. Lumber puncture was performed in 96% of cases and resulted in the detection of 4 cases of unsuspected meningitis, one of which was bacterial. 2 children had normal lumbar punctures on admission but developed meningococcal meningitis within 48 hours. Sugar, calcium, urea, and electrolyte estimations, and blood counts were commonly performed but were unhelpful. We suggest that lumbar puncture in those children presenting with their first febrile convulsion under the age of 18 months is the only useful routine investigation.     

Neonatal pattern of breathing during active and quiet sleep after maternal administration of meperidine.

The aim of this study was to reappraise the effects of maternal meperidine administration on breathing pattern during the first hours of life taking into account the state of alertness. Because breathing instability is more pronounced during active sleep, we hypothesized that meperidine administration might create a greater risk for respiratory instability during active sleep, the prominent sleep state in newborns. We studied eight full-term, healthy newborns whose mothers had received a continuous i.v. infusion of meperidine (81 +/- 9 mg) that was terminated 5.5 +/- 2.1 h before delivery. These infants were compared with a control group of eight full-term newborns whose mothers did not receive any opioids. In both groups, all babies were delivered vaginally after a normal labor and had Apgar scores of 9 or 10 at 1 and 5 min. Neonatal gastric secretion and maternal venous and umbilical venous blood were sampled at delivery for determination of meperidine concentration. From 60 to 300 min after delivery, behavioral sleep states and thoracic and abdominal movement as well as transcutaneous arterial oxygen saturation (SaO2) were monitored continuously. The number of apneic spells lasting more than 3 s during 100 min of recording and the percentage of time with SaO2 below 90% in each sleep state were recorded. During quiet sleep, all respiratory variables were similar in both groups. During active sleep, there were significantly more apneic episodes (37.1 +/- 25.1 versus 11.2 +/- 13.9) and a higher percentage of time with SaO2 less than 90% (14.3 +/- 16.7% versus 1.3 +/- 1.5%) in the meperidine group than in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin K deficiency, intracranial hemorrhage, and a subgaleal hematoma: a fatal combination.

An exclusively breast-fed infant, who did not receive vitamin K prophylaxis at birth, presented with signs of raised intracranial pressure. Her clinical course was compounded by a lumbar puncture, which revealed blood in the cerebrospinal fluid, and a large subgaleal hematoma, which developed at the puncture site of an attempted scalp vein catheterization, resulting in coning, hypovolemic shock, and death. A major coagulopathy was present, probably caused by vitamin K deficiency. The necessity for vitamin K prophylaxis in all newborns and the timing of lumbar puncture in the critically ill child are discussed.     

Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children

OBJECTIVE: We have used the combination of midazolam, a short-acting benzodiazepine, and ketamine, a "dissociative anesthetic," to provide conscious sedation for invasive or lengthy procedures. METHODS: A total of 350 procedures (74 lumbar punctures, 97 bone marrow aspirations or biopsies, 84 radiotherapy sessions, and 95 imaging studies) were performed on 68 children, 4 months to 17 years of age, in both inpatient and ambulatory settings. All patients had an intravenous line in place and were monitored for heart rate and O2 saturation by pulse oximetry for the duration of the procedure and recovery time. Blood pressure was monitored periodically (every 5 to 30 minutes). Oxygen and suction equipment was available during the procedure. In addition to the individual performing the procedure, a second staff member trained in airway management (eg, physician, nurse practitioner, or registered nurse) was present to monitor vital signs and respiratory status. Patients were sedated initially with midazolam (0.05 to 0.1 mg/kg intravenously; maximum single dose of 2 mg, maximum total dose of 4 mg), followed by ketamine (1 to 2 mg/kg intravenously). During lengthy procedures, additional doses of ketamine (0.5 to 1 mg/kg) were given as necessary. Effectiveness of the sedation, recovery time, and adverse events associated with the sedative regimen were documented. RESULTS: All patients were effectively sedated with this regimen. Four patients experienced transient decrease in O2 saturation (<85%) requiring temporary interruption of the procedure and oxygen by blow-by; the procedure was subsequently completed without incident in each case. Two patients experienced significant agitation during recovery from sedation. This side effect resolved spontaneously after 5 to 10 minutes in one patient and was effectively treated with diphenhydramine hydrochloride in the other. Twenty-four lumbar punctures were associated with transient decrease in O2 saturation (88% to 92%), which improved by relief of neck flexion and/or blow-by oxygen. No hypotension, bradycardia, or respiratory depression requiring respiratory support or reversal of sedation was noted. Anesthesia recovery time ranged from <15 minutes to 120 minutes with >70% of patients recovering within 30 minutes. Most patients demonstrated an increase in oral secretions requiring occasional suctioning. Transient sleep disturbances were reported in only two patients. CONCLUSIONS: This sedative regimen of intravenous midazolam and ketamine was found to be safe and effective. Its use has greatly reduced patient and parent anxiety for diagnostic and therapeutic procedures.     

Auf dem Weg zur schmerzarmen Kinderklinik

Avoiding or reducing the pain experienced by inpatient children and adolescents during medical procedures is an issue of growing importance. To what extent the daily clinical routine has changed is unclear. In order to ascertain this we developed a six-page questionnaire and sent it to 424?facilities in Germany, 49 in Austria and nine in German-speaking Switzerland that carry out neuropaediatric procedures. We also contacted so-called social paediatric centres in Germany. The enquiry period was from June 2008 to January 2009. The return rate was 54% (Germany 55%, Austria 40%, Switzerland 66%). We found clear differences in the handling of painful procedures between the different countries as well as between various facilities. While in Switzerland and Austria use of EMLA (eutectic mixture of local anesthetics) is routine for taking blood samples or venous catheter insertion, and in Austria also for lumbar puncture, only a quarter of all facilities in Germany use EMLA cream ??often?? or ??routinely?? for blood tests, whereby its use largely depends on the physician in charge, especially at university clinics. Nevertheless, German physicians appear to be unsatisfied with the current status of EMLA usage. In all, 60% of the doctors surveyed at university clinics would prefer to see more frequent use of EMLA cream for their patients. Three quarters of the responding clinics use local anaesthesia ??almost always?? or ??often?? for lumbar puncture. The ratio increases significantly if the clinic has guidelines for pain management in place. The recommended EMLA application time of 60?min is adhered to by less than one-fifth of German physicians.     

Analgesia with saccharose during heel capillary prick. A randomized study in 37 newborns of over 33 weeks of amenorrhea]

BACKGROUND: To evaluate the efficiency of intraoral saccharose administration for analgesia among neonates born after at least 33 weeks of gestation. POPULATION AND METHOD: Thirty-seven neonates from two neonatal units were tested using an objective scale of infants' pain. A double blind study of the heel prick response after saccharose vs. water administration was performed. RESULTS: Prior administration of saccharose significantly reduced the pain reaction (1.24 vs. 2.24, P < 10(-5)). CONCLUSION: The analgesia obtained after an intraoral saccharose administration can be useful for repeated punctures for which common procedures of analgesia are ineffective. Beyond its use for heel prick, this procedure could be proposed for venous punctures when ELMA analgesia is not possible.